Monolithic MHz-frame rate digital SiPM-IC with sub-100 ps precision and 70 μ~\mum pixel pitch

This paper presents the design and characterization of a monolithic integrated circuit (IC) including digital silicon photomultipliers (dSiPMs) arranged in a 32$~\times~$32 pixel matrix at 70$~\mu$m pitch. The IC provides per-quadrant time stamping and hit-map readout, and is fabricated in a standard 150-nm CMOS technology. Each dSiPM pixel consists of four single-photon avalanche diodes (SPADs) sharing a quenching and subsequent processing circuitry and has a fill factor of 30$~\%$. A sub-100$~$ps precision, 12-bit time-to-digital converter (TDC) provides timestamps per quadrant with an acquisition rate of 3$~$MHz. Together with the hit map, the total sustained data throughput of the IC amounts to 4$~$Gbps. Measurements obtained in a dark, temperature-stable environment as well as by using a pulsed laser environment show the full dSiPM-IC functionality. The dark-count rate (DCR) as function of the overvoltage and temperature, the TDC resolution, differential and integral nonlinearity (DNL/INL) as well as the propagation-delay variations across the matrix are presented. With aid of additional peripheral test structures, the main building blocks are characterized and key parameters are presented.Comment: 16 pages, 13 figures, 1 tabl

Study of Δ(1232)\Delta(1232) isobar electroproduction at VEPP-2M e+e−e^+e^- collider

Results from the Spherical Nonmagnetic Detector (SND) on $\Delta (1232)$ isobar electroproduction in the collisions of beam electrons (positrons) and residual gas nuclei in the VEPP-2M $e^+e^-$ collider are presented. On the basis of the obtained data the expected counting rate of this process in future high luminosity $e^+e^-$ colliders (~$\phi$-, $c$-$\tau$- and $b$-factories) was estimated.Comment: 7 pages LATEX and 3 figure

Minimization of phonon-tunneling dissipation in mechanical resonators

Micro- and nanoscale mechanical resonators have recently emerged as ubiquitous devices for use in advanced technological applications, for example in mobile communications and inertial sensors, and as novel tools for fundamental scientific endeavors. Their performance is in many cases limited by the deleterious effects of mechanical damping. Here, we report a significant advancement towards understanding and controlling support-induced losses in generic mechanical resonators. We begin by introducing an efficient numerical solver, based on the "phonon-tunneling" approach, capable of predicting the design-limited damping of high-quality mechanical resonators. Further, through careful device engineering, we isolate support-induced losses and perform the first rigorous experimental test of the strong geometric dependence of this loss mechanism. Our results are in excellent agreement with theory, demonstrating the predictive power of our approach. In combination with recent progress on complementary dissipation mechanisms, our phonon-tunneling solver represents a major step towards accurate prediction of the mechanical quality factor.Comment: 12 pages, 4 figure

Deregulation of apoptosis mediators' p53 and bcl2 in lung tissue of COPD patients

Abnormal apoptotic events in chronic obstructive pulmonary disease (COPD) subvert cellular homeostasis and may play a primary role in its pathogenesis. However, studies in human subjects are limited

Marked alveolar apoptosis/proliferation imbalance in end-stage emphysema

BACKGROUND: Apoptosis has recently been proposed to contribute to the pathogenesis of emphysema. METHODS: In order to establish if cell fate plays a role even in end-stage disease we studied 16 lungs (9 smoking-associated and 7 α1antitrypsin (AAT)-deficiency emphysema) from patients who had undergone lung transplantations. Six unused donor lungs served as controls. Apoptosis was evaluated by TUNEL analysis, single-stranded DNA laddering, electron microscopy and cell proliferation by an immunohistochemical method (MIB1). The role of the transforming growth factor (TGF)-β1 pathway was also investigated and correlated with epithelial cell turnover and with the severity of inflammatory cell infiltrate. RESULTS: The apoptotic index (AI) was significantly higher in emphysematous lungs compared to the control group (p ≤ 0.01), particularly if only lungs with AAT-deficiency emphysema were considered (p ≤ 0.01 vs p = 0.09). The proliferation index was similar in patients and controls (1.9 ± 2.2 vs 1.7 ± 1.1). An increased number of T lymphocytes was observed in AAT-deficiency lungs than smoking-related cases (p ≤ 0.05). TGF-β1 expression in the alveolar wall was higher in patients with smoking-associated emphysema than in cases with AAT-deficiency emphysema (p ≤ 0.05). A positive correlation between TGF-βRII and AI was observed only in the control group (p ≤ 0.005, r(2 )= 0.8). A negative correlation was found between the TGF-β pathway (particularly TGF-βRII) and T lymphocytes infiltrate in smoking-related cases (p ≤ 0.05, r(2 )= 0.99) CONCLUSION: Our findings suggest that apoptosis of alveolar epithelial cells plays an important role even in end-stage emphysema particularly in AAT-deficiency disease. The TGFβ-1 pathway does not seem to directly influence epithelial turnover in end-stage disease. Inflammatory cytokine different from TGF-β1 may differently orchestrate cell fate in AAT and smoking-related emphysema types

Design and Factory Test of the E /E- Frascati Linear Accelerator for DAFNE

The electron-positron accelerator for the DAFNE project has been built and is in test at Titan Beta in Dublin, CA. This S-Band RF linac system utilizes four 45 MW sledded klystrons and 16-3 m accelerating structures to achieve the required performance. It delivers a 4 ampere electron beam to the positron converter and accelerates the resulting positrons to 550 MeV. The converter design uses a 4.3T pulsed tapered flux compressor along with a pseudo-adiabatic tapered field to a 5 KG solenoid over the first two positron accelerating sections. Quadrupole focusing is used after 100 MeV. The system performance is given in Table 1. This paper briefly describes the design and development of the various subassemblies in this system and gives the initial factory test data

PPARα downregulates airway inflammation induced by lipopolysaccharide in the mouse

BACKGROUND: Inflammation is a hallmark of acute lung injury and chronic airway diseases. In chronic airway diseases, it is associated with profound tissue remodeling. Peroxisome proliferator-activated receptor-α (PPARα) is a ligand-activated transcription factor, that belongs to the nuclear receptor family. Agonists for PPARα have been recently shown to reduce lipopolysaccharide (LPS)- and cytokine-induced secretion of matrix metalloproteinase-9 (MMP-9) in human monocytes and rat mesangial cells, suggesting that PPARα may play a beneficial role in inflammation and tissue remodeling. METHODS: We have investigated the role of PPARα in a mouse model of LPS-induced airway inflammation characterized by neutrophil and macrophage infiltration, by production of the chemoattractants, tumor necrosis factor-α (TNF-α), keratinocyte derived-chemokine (KC), macrophage inflammatory protein-2 (MIP-2) and monocyte chemoattractant protein-1 (MCP-1), and by increased MMP-2 and MMP-9 activity in bronchoalveolar lavage fluid (BALF). The role of PPARα in this model was studied using both PPARα-deficient mice and mice treated with the PPARα activator, fenofibrate. RESULTS: Upon intranasal exposure to LPS, PPARα(-/- )mice exhibited greater neutrophil and macrophage number in BALF, as well as increased levels of TNF-α, KC, MIP-2 and MCP-1, when compared to PPARα(+/+ )mice. PPARα(-/- )mice also displayed enhanced MMP-9 activity. Conversely, fenofibrate (0.15 to 15 mg/day) dose-dependently reduced the increase in neutrophil and macrophage number induced by LPS in wild-type mice. In animals treated with 15 mg/day fenofibrate, this effect was associated with a reduction in TNF-α, KC, MIP-2 and MCP-1 levels, as well as in MMP-2 and MMP-9 activity. PPARα(-/- )mice treated with 15 mg/day fenofibrate failed to exhibit decreased airway inflammatory cell infiltrate, demonstrating that PPARα mediates the anti-inflammatory effect of fenofibrate. CONCLUSION: Using both genetic and pharmacological approaches, our data clearly show that PPARα downregulates cell infiltration, chemoattractant production and enhanced MMP activity triggered by LPS in mouse lung. This suggests that PPARα activation may have a beneficial effect in acute or chronic inflammatory airway disorders involving neutrophils and macrophages